Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer’s disease (AD). It remains unknown whether sTREM2 regulates the pathogenesis of AD. Here we identified transgelin-2 (TG2) expressed on neurons as the receptor for sTREM2. The microglia-derived sTREM2 binds to TG2, induces RhoA phosphorylation at S188, and deactivates the RhoA-ROCK-GSK3β pathway, ameliorating tau phosphorylation. The sTREM2 (77-89) fragment, which is the minimal active sequence of sTREM2 to activate TG2, mimics the inhibitory effect of sTREM2 on tau phosphorylation. Overexpression of sTREM2 or administration of the active peptide rescues tau pathology and behavioral defects in the tau P301S transgenic mice. Together, these findings demonstrate that the sTREM2-TG2 interaction mediates the cross-talk between microglia and neurons. sTREM2 and its active peptide may be a potential therapeutic intervention for tauopathies including AD.

Autoimmune encephalitis (AE) is increasingly recognized as a cause of brain disorders that greatly benefit from immunotherapy. Starting treatment quickly and increasing the use of immunotherapy can lead to better results for AE patients. Currently, there are standardized treatment guidelines for treating AE. First-line therapy includes intravenous corticosteroids, plasma exchange, and intravenous immunoglobulin. Second-line therapy involves rituximab, cyclophosphamide, mycophenolate mofetil, and azathioprine. Third-line therapy uses agents that deplete plasma cells (bortezomib, daratumumab, and obinutuzumab), drugs that modulate cytokines (tocilizumab, anakinra, tofacitinib, and interleukin-2), and treatments that target intrathecal immune cells (intrathecal methotrexate). This review aims to summarize the immunotherapeutic strategies available for treating AE and provide an update on refractory AE.

Homocysteine (Hcy) is an important metabolite in methionine metabolism. When the metabolic pathway of homocysteine is abnormal, it will accumulate in the body and eventually lead to hyperhomocysteinemia. In recent years, many studies have found that hyperhomocysteinemia is related to the occurrence and development of Parkinson's disease. This study reviews the roles of homocysteine in the pathogenesis of Parkinson's disease and illustrates the harmful effects of hyperhomocysteinemia on Parkinson's disease.

Background: To scrutinize the relationship between vitamin B2 consumption and cognitive function based on the NHANES database. Methods: This cross-sectional study included eligible older adults from the NHANES 2011–2014. Vitamin B2 intake was determined from dietary interview data for two 24-h periods. Cognitive function was evaluated through the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The regression analyses were used to evaluate the association of vitamin B2 intake with cognitive performance. Stratified analyses based on gender, race, and body mass index (BMI) were conducted. Results: Higher vitamin B2 intake was correlated with higher scores on each test. As compared to the lowest quartile, the highest quartile of vitamin B2 intake was related to a 45.1-fold increase (P = 0.004) on the DSST test sores. Moreover, those who were males, non-Hispanic whites, or had a BMI of 18.5 to 30 kg/m² had a stronger relationship between total vitamin B2 consumption and cognitive function. Conclusion: It's possible that older persons who consume more vitamin B2 have enhanced performance in some areas of cognitive function. To determine the causal link between vitamin B2 consumption and cognitive performance, further long-term research is required.

The aggregation of α‐synuclein plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Epidemiological evidence indicates that high level of homocysteine (Hcy) is associated with an increased risk of PD. However, the molecular mechanisms remain elusive. Here, we report that homocysteine thiolactone (HTL), a reactive thioester of Hcy, covalently modifies α‐synuclein on the K80 residue. The levels of α‐synuclein K80Hcy in the brain are increased in an age‐dependent manner in the TgA53T mice, correlating with elevated levels of Hcy and HTL in the brain during aging. The N‐homocysteinylation of α‐synuclein stimulates its aggregation and forms fibrils with enhanced seeding activity and neurotoxicity. Intrastriatal injection of homocysteinylated α‐synuclein fibrils induces more severe α‐synuclein pathology and motor deficits when compared with unmodified α‐synuclein fibrils. Increasing the levels of Hcy aggravates α‐synuclein neuropathology in a mouse model of PD. In contrast, blocking the N‐homocysteinylation of α‐synuclein ameliorates α‐synuclein pathology and degeneration of dopaminergic neurons. These findings suggest that the covalent modification of α‐synuclein by HTL promotes its aggregation. Targeting the N‐homocysteinylation of α‐synuclein could be a novel therapeutic strategy against PD.